The HDAC7-TET2 epigenetic axis is essential during early B lymphocyte development
In: Nucleic Acids Research, 2022-08-26
Online
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Zugriff:
Correct B cell identity at each stage of cellular differentiation during B lymphocyte development is critically dependent on a tightly controlled epigenomic landscape. We previously identified HDAC7 as an essential regulator of early B cell development and its absence leads to a drastic block at the pro-B to pre-B cell transition. More recently, we demonstrated that HDAC7 loss in pro-B-ALL in infants associates with a worse prognosis. Here we delineate the molecular mechanisms by which HDAC7 modulates early B cell development. We find that HDAC7 deficiency drives global chromatin de-condensation, histone marks deposition and deregulates other epigenetic regulators and mobile elements. Specifically, the absence of HDAC7 induces TET2 expression, which promotes DNA 5-hydroxymethylation and chromatin de-condensation. HDAC7 deficiency also results in the aberrant expression of microRNAs and LINE-1 transposable elements. These findings shed light on the mechanisms by which HDAC7 loss or misregulation may lead to B cell-based hematological malignancies.
Spanish Ministry of Economy and Competitiveness (MINECO) [SAF2017-87990-R]; Spanish Ministry of Science and Innovation (MICINN) [EUR2019-103835]; Josep Carreras Leukemia Research Institute (IJC, Badalona, Barcelona); IDIBELL Research Institute (L’Hospitalet de Llobregat, Barcelona); A.M. is funded by the Spanish Ministry of Science, Innovation and Universities, which is part of the Agencia Estatal de Investigacion (AEI) [PRE2018-083183] (cofunded by the European Social Fund]; OdB. was funded by a Juan de la Cierva Formacion Fellowship ´ from the Spanish Ministry of Science, Innovation and Universities [FJCI-2017-32430]; Postdoctoral Fellowship from the Asociacion Espa ´ nola Contra el C ˜ ancer (AECC) ´ Foundation [POSTD20024DEBA]; B.M. is awardee of the Ayudas para la formacion del profesorado universitario ´[FPU18/00755, Ministerio de Universidades]; B.M.J. is funded by La Caixa Banking Foundation Junior Leader project [LCF/BQ/PI19/11690001]; FEDER/Spanish Ministry of Science and Innovation [RTI2018-094788-A-I00]; L.T.-D. is funded by the FPI Fellowship [PRE2019-088005]; L.R. is funded by an AGAUR FI fellowship [2019FI-B00017]; J.L.S. is funded by ISCIII [CP19/00176], co-funded by ESF, ‘Investing in your future’ and the Spanish Ministry of Science, Innovation and Universities [PID2019-111243RA-I00]. CRG acknowledge the support of the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049- S, MCIN/AEI /10.13039/501100011033). Funding for open access charge: Spanish Ministry of Science, Innovation and Universities (MICIU) [SAF2017-87990-R, EUR2019-103835].
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The HDAC7-TET2 epigenetic axis is essential during early B lymphocyte development
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Autor/in / Beteiligte Person: | Azagra, Alba ; Meler, Ainara ; Oriol de Barrios ; Tomás-Daza, Laureano ; Collazo, Olga ; Monterde, Beatriz ; Obiols, Mireia ; Rovirosa, Llorenç ; Vila-Casadesús, Maria ; Cabrera-Pasadas, Mónica ; Gusi-Vives, Mar ; Graf, Thomas ; Varela, Ignacio ; José Luis Sardina ; Biola M Javierre ; Parra, Maribel ; Ministerio de Ciencia, Innovación y Universidades (España) ; Agencia Estatal de Investigación (España) ; Josep Carreras Leukemia Foundation ; Asociación Española Contra el Cáncer ; Fundación 'la Caixa' ; Instituto de Salud Carlos, III |
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Zeitschrift: | Nucleic Acids Research, 2022-08-26 |
Veröffentlichung: | Oxford University Press, 2022 |
Medientyp: | unknown |
ISSN: | 1362-4962 (print) ; 0305-1048 (print) |
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